Renal adverse effects following the use of different immune checkpoint inhibitor regimens: A real-world pharmacoepidemiology study of post-marketing surveillance data.
BACKGROUNDS: Although kidney impairments have been reported following immune checkpoint inhibitors (ICIs) in clinical studies, there are few pharmacoepidemiology studies to compare the occurrences, clinical features, and prognosis of renal adverse effects.
METHODS: Disproportionality and Bayesian analysis were used in data mining to screen the suspected renal adverse effects after the administration of different ICIs, based on FDA's Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset, fatality and hospitalization rates of renal adverse effects were also investigated.
RESULTS: We identified 1444 reports of renal adverse effects. Affected patients tended to be older than 65 years (52.7%). Renal effects were most commonly reported in nivolumab monotherapy (33.24%). Atezolizumab appeared the strongest association among six ICI monotherapies, based on the highest reporting odds ratio (ROR = 144.38, two-sided 95% CI = 123.08 -169.37), proportional reporting ratio (PRR = 139.13, chi(2) = 21 425.38), and empirical Bayes geometric mean (EBGM = 131.75, one-sided 95% CI = 115.28). The combination treatments showed higher RORs, PRRs, and EBGMs, compared with either nivolumab or pembrolizumab monotherapy. The median onset time of renal adverse effects was 48 (interquartile range [IQR] 18.75-121.25) days after the monotherapies of ICI regimens. Patients treated with the combination of nivolumab plus ipilimumab were younger than receivers in nivolumab monotherapy (63.81 +/- 12.03 vs 66.39 +/- 11.53, P = .004); The fatality rate of renal adverse effects appeared lower in the combination group, compared to nivolumab monotherapy (18.53% vs 27.50%, P = .004). The top hospitalization rates due to renal effects occurred in patients with combination therapies.
CONCLUSION: Based on the FAERS database, we profiled renal adverse effects after various ICIs with real-world data in occurrences, clinical characteristics, and prognosis. Renal effects should be tightly monitored, especially within the first several months after ICIs administration. Particular concern should be paid for patients with a tendency for kidney impairments, such as old age.
|投稿者||Chen, Gang; Qin, Yan; Fan, Qian-Qian; Zhao, Bin; Mei, Dan; Li, Xue-Mei|
|組織名||Nephrology Department, Peking Union Medical College Hospital, Peking Union;Medical College, Chinese Academy of Medical Sciences, Beijing, China.;Pharmacy Department, Peking Union Medical College Hospital, Peking Union Medical;College, Chinese Academy of Medical Sciences, Beijing, China.|